<i>Dax1</i>Expression Is Dependent on Steroidogenic Factor 1 in the Developing Gonad

Hoyle, Charles H.V.; Narváez, Véronica; Alldus, Graham; Lovell-Badge, Robin; Swain, Amanda

doi:10.1210/mend.16.4.0802

Cited by 42 publications

(3 citation statements)

References 35 publications

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“…Additional lengths of promoter to 3000 bp did not result in increased activity (data not shown). Previous work had shown the nuclear receptor Sf1 bound to two sites within this region to induce Dax1 expression in steroidogenic tissues, at −80 bp and −128 bp from the Dax1 ATG (8–10). However, Sf1 mRNA and protein are not detectable in mES cells (data not shown).…”

Section: Resultsmentioning

confidence: 99%

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LRH-1 and Nanog regulate Dax1 transcription in mouse embryonic stem cells

Kelly¹,

Hammer²

2011

Molecular and Cellular Endocrinology

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Dax1, an atypical orphan nuclear receptor expressed in steroidogenic tissues, has recently been shown to be expressed in mouse embryonic stem (mES) cells and is required for pluripotency. While the mechanisms of transcriptional regulation of Dax1 in steroidogenic organs have been well characterized, those in mES cells have not. Here we report that only 500 bp of the Dax1 gene promoter sequence are needed to drive expression in mES cells. In steroidogenic tissues, NR5A1 (Sf1) binds to nuclear receptor binding sites within this sequence to regulate Dax1 expression. In mES cells, while NR5A1 (Sf1) is not expressed, NR5A2 (LRH-1) expression is robust. Luciferase assays, EMSA and overexpression/knockdown studies demonstrate that LRH-1 binds the −128 site and regulates Dax1 in mES cells. Predicated on recent work indicating that Nanog binds to the Dax1 intron, we have used chromatin immunoprecipitation experiments (ChIP) to define an intronic site that is bound by Nanog. Overexpression and knockdown of Nanog in mES cells result in alteration of Dax1 expression, and luciferase assays reveal that this sequence can enhance transcription of a Dax1 reporter construct. These data indicate that LRH-1 and Nanog cooperate to regulate Dax1 expression in mES cells.

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Section: Resultsmentioning

confidence: 99%

“…Steroidogenic factor 1 (Sf1) has been shown to bind to two sites within the proximal promoter of Dax1 (8–10). The Wnt pathway transcriptional mediator, β-catenin, in complex with Sf1 activates Dax1 transcription, and indeed Wnt4 knockout mice have reduced expression of Dax1 in the female gonad (11).…”

Section: Introductionmentioning

confidence: 99%

LRH-1 and Nanog regulate Dax1 transcription in mouse embryonic stem cells

Kelly¹,

Hammer²

2011

Molecular and Cellular Endocrinology

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“…DAX-1 represses the transcriptional activities of both SF-1/Ad4BP and LRH-1 via these NR boxes [20, 90]. Tissue localization of DAX-1 is very similar to SF-1/Ad4BP [85, 91], probably due to the fact that SF-1/Ad4BP regulates DAX-1 expression by direct binding to the promoter and enhancer regions at least during fetal life [85, 91, 92]. Therefore, ovarian DAX-1 is detectable in both granulosa and theca cells [85, 93].…”

Section: Regulation Of Nr0b1/dax-1 (Dosage Sensitive Sex Reversalmentioning

confidence: 99%

Transcriptional Regulation of Ovarian Steroidogenic Genes: Recent Findings Obtained from Stem Cell-Derived Steroidogenic Cells

Yazawa

Imamichi

Sekiguchi

et al. 2019

BioMed Research International

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Ovaries represent one of the primary steroidogenic organs, producing estrogen and progesterone under the regulation of gonadotropins during the estrous cycle. Gonadotropins fluctuate the expression of various steroidogenesis-related genes, such as those encoding steroidogenic enzymes, cholesterol deliverer, and electronic transporter. Steroidogenic factor-1 (SF-1)/adrenal 4-binding protein (Ad4BP)/NR5A1 and liver receptor homolog-1 (LRH-1) play important roles in these phenomena via transcriptional regulation. With the aid of cAMP, SF-1/Ad4BP and LRH-1 can induce the differentiation of stem cells into steroidogenic cells. This model is a useful tool for studying the molecular mechanisms of steroidogenesis. In this article, we will provide insight into the transcriptional regulation of steroidogenesis-related genes in ovaries that are revealed from stem cell-derived steroidogenic cells. Using the cells derived from the model, novel SF-1/Ad4BP- and LRH-1-regulated genes were identified by combined DNA microarray and promoter tiling array analyses. The interaction of SF-1/Ad4BP and LRH-1 with transcriptional regulators in the regulation of ovarian steroidogenesis was also revealed.

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Molecular characterization of the Bidder's organ in the cane toad (Bufo marinus)

2010

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In toads, both males and females develop a unique gonadal structure called the Bidder's organ (BO), which resembles ovarian tissue and is attached to the anterior part of the gonad. It is not clear whether the BO is a vestigial organ, or has an endocrine function. In this study, we investigated the expression of the gonadal development genes Dmrt1, Sox9, Sf1, Dax1, and p450arom in the developing BO as compared with the gonads of male and female cane toads. We demonstrate that Sf1, Dax1, and p450arom, key genes involved in vertebrate steroidogenesis, are transcriptionally active in the BO during developmental milestones associated with sexual development and maturation. Furthermore, the pattern of transcriptional activity in the BO is completely independent of the corresponding gonads in both sexes, despite its ovary-like morphology. These results suggest that the BO likely has a steroidogenic role in the development of the cane toad, distinct from that of the gonads.

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Dax1Expression Is Dependent on Steroidogenic Factor 1 in the Developing Gonad

Cited by 42 publications

References 35 publications

LRH-1 and Nanog regulate Dax1 transcription in mouse embryonic stem cells

LRH-1 and Nanog regulate Dax1 transcription in mouse embryonic stem cells

Transcriptional Regulation of Ovarian Steroidogenic Genes: Recent Findings Obtained from Stem Cell-Derived Steroidogenic Cells

Molecular characterization of the Bidder's organ in the cane toad (Bufo marinus)

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